Table 1 Association of glycated hemoglobin levels with atrial fibrillation-related outcomes

AF development

Αune, D. et al., 2015 [14]

Increased incidence of AF in diabetic patients:

Meta-analysis

RR: 1.30, 95% (CIs 1.03–1.66)

Increased incidence of AF in diabetic patients per 20 mg/dl increase of blood glucose:

RR: 1.11 (95% CIs 1.04–1.18)

Zhao H. et al., 2020 [52]

Increased incidence of AF in diabetic and non-diabetic patients per 1% increase of HbA1c:

Meta-analysis

RR: 1.16 (95% CI 1.07–1.27)

Qi W. et al., 2017 [51]

Increased incidence of AF in diabetic patients per 1% increase of HbA1c:

Meta-analysis

RR: 1.13, 95% (CIs 1.09–1.18)

Huxley, R.R. et al., 2012 [88]

Increased incidence of AF in diabetics with poor glycemic control:

Original research

HR: 1.13, (95% CIs 1.07–1.20) per 1% point increase of HbA1c

Iguchi, Y. et al., 2012 [89]

Elevating HbA1c associated with higher prevalence of AF:

Original research

OR: 1.18 (95% Cis 1.09–1.28)

Dublin, S. et al., 2010 [90]

Higher risk for developing AF in individuals with worse glycemic control compared to those without DM:

Original research

HbA1c ≤ 7: adjusted OR: 1.06 (95% CI 0.74–1.51)

7 < HbA1c < 8: adjusted OR: 1.48 (95% CI 1.09–2.01)

8 < HbA1c < 9: adjusted OR: 1.46 (95% CI 1.02–2.08)

HbA1c > 9: adjusted OR: 1.96 (95% CI 1.22–3.14)

Fatemi, O. et al., 2014 [91]

Intensive glycemic control not affecting the risk of AF incidence:

Original research

Incident AF occurred in 159 patients (1.58%) over the follow-up period at a rate of 5.9/1,000 person-years in the intensive-therapy group (targeting at HbA1c < 6.0%), and at a rate of 6.37/1,000 person-years in the standard-therapy group (targeting at 7% < HbA1c < 7.9%) (p = 0.52)

Ahmadi, SS. et al., 2020 [10]

Increased incidence of AF in diabetic individuals compared with age- and sex-matched controls

Original research

aHR: 1.28 (95% CIs 1.26–1.30)

Risk of stroke

Saliba, W. et al., 2015 [70]

Increased risk of stroke among AF patients with higher HbA1c levels in comparison with patients without DM:

Original research

HbA1c < 6.35% HR: 1.04, 95% CI 0.83–1.30

HbA1c 6.35–6.90% HR:1.14, 95% CI 0.92–1.42)

HbA1c 6.91–7.70% HR: 1.46, 95% CI 1.19–1.79

HbA1c > 7.70% HR: 1.63, 95% CI 1.33–2.00

Among AF patients with DM, HR: 1.17 (95% CI 1.09–1.26) for every 1% increment in HbA1c

The AUC was 0.585 for the CHA2DS2-VASc score, which increased to 0.604 when HbA1c was included in the model (p = 0.038)

Fangel MV. et al., 2019 [69]

Increased risk of stroke among AF patients with higher HbA1c levels

Original research

• aHR: 1.49 (95% CIs: 1.09–2.05) for patients with HbA1c = 49–58 mmol/mol compared to HbA1c ≤ 48 mmol/mol

• aHR: 1.59 (95% CI 1.13–2.22): for patients with HbA1c > 58 mmol/mol compared to HbA1c ≤ 48 mmol/mol

Chan, YH. et al., 2020 [71]

Increased risk of ischemic stroke/thromboembolism among AF patients with higher HbA1c levels:

Original research

Compared with patients with an HbA1c level of < 5.4%, the risk significantly increased when HbA1c levels were higher than 6.5%

• aHR: 1.20 (95% CIs 1.00–1.43) for HbA1c level of 6.5–6.9%

• aHR: 1.32 (95% CIs 1.11–1.57) for HbA1c level of 7.0–7.9%, and

• aHR: 1.48 (95% CI 1.25–1.76) for HbA1c level of ≥ 8.0%

Risk of mortality or hospitalizations

Papazoglou AS. et al., 2021 [21]

Risk of all-cause mortality among diabetic AF patients depending on HbA1c levels:

Original research

HbA1c levels above 7.6% and below 6.2% have been proposed as markers of increased and decreased mortality, respectively

Kanellopoulou K. et al. 2018 [24]

Increased risk of all-cause mortality among diabetic AF patients with higher HbA1c levels:

Original research

. The mortality for AF patients with stroke history is increased with the increase of HbA1c in patients with DM in a statistically significant manner (p < 0.001). A non-significant increase in mortality was observed in patients without DM. (p = 0.22)

Selvin E. et al. 2010 [78]

J-shaped association between HbA1c and the risk of all-cause mortality among individuals without DM:

Original research

• HbA1c < 5.0%: aHR: 1.48 (95% CIs1.21–1.81)

• HbA1c = 5.0 to < 5.5% (reference): aHR: 1.00 (95% CIs 1.00–1.00)

• HbA1c = 5.5 to < 6.0%: aHR: 1.19 (95% CIs 1.05–1.35)

• HbA1c = 6.0 to < 6.5%: 1.61 (1.35–1.91)

• HbA1c ≥ 6.5%: aHR: 1.71 (95% CIs 1.30–2.25)

Li W. et al., 2016 [79]

J-shaped association between HbA1c and the risk of all-cause mortality among patients with DM:

Original research

• HbA1c < 6.0%: aHR: 1.06 (95% CIs0.92–1.24)

• HbA1c = 6.0 to < 6.9% (reference): aHR: 1.00

• HbA1c = 7.0 to < 7.9%: aHR: 1.10 (95% CI 0.92–1.30)

• HbA1c = 8.0 to < 8.9%: 0.93 (95% CI 0.75–1.16)

• HbA1c = 9.0 to < 0.9%: 1.26 (95% CI 1.01–1.58)

• HbA1c = 10.0 to < 10.9%: 1.18 (95% CI 0.93–1.51)

• HbA1c ≥ 11.0%: aHR: 1.31 (95% CI1.08–1.60)

AF ablation success

Lu, Z.H. et al., 2015 [86]

Higher levels of HbA1c associated with increased risk of AF recurrence of atrial tachyarrhythmia in DM patients undergoing catheter ablation:

Original research

• HbA1c < 6.9%: success rate of ablation was 69.0%

HbA1c ≥ 6.9%: success rate of ablation 46.8% (p = 0.004)

• HbA1c was independent predictor of recurrent atrial tachyarrhythmia: aHR: 1.22, 95% CI 1.02–1.47

• HbA1c cut-off value of ≥ 6.9% predicted AF recurrence with 55.0% sensitivity and 67.4% specificity (AUC = 0.634)

Donnellan E. et al., 2019 [85]

Better outcomes of AF catheter ablation with improvement of pre-procedural HbA1c levels:

Original research

Improvement of HbA1c levels 12 months prior to ablation by more than 10% was independently associated with 30% decreased risk of AF recurrence. 68.75% of patients with HbA1c > 9% at the time of ablation developed recurrent AF, compared with 32.4% of those with HbA1c < 7% (p < 0.0001)

Stout KM. et al., 2021 [92]

Increased risk of recurrent atrial arrhythmias and cardiovascular hospitalizations following AF ablation with higher HbA1c levels:

Original research

HR: 1.57 (95% CIs 1.02–2.36)